Chagas' disease, caused by infection with the hemoflagellate Trypanosoma cruzi is responsible for an estimated 45,000 deaths annually, with 16 to 18 million people estimated to be infected with the parasite and almost eight times that number at risk for exposure. The disease is strictly limited to the western hemisphere, with the majority of identified human cases found in South and Central America. There is currently no effective treatment for infected persons. The status of this disease within the United States presents an interesting paradox. There have been very few cases of locally acquired T. cruzi infection reported in humans in the United States. However, multiple published studies, as well as, our own preliminary results indicate that the sylvatic cycle of T. cruzi infection is well established in the southern portion of Texas, as well as, other areas of the United States. We hypothesize that one or more of four circumstances may contribute to this discrepancy: 1) Domestic strains of T. cruzi are relatively non-pathogenic; 2) The prevalence of the infection is under-diagnosed because of difficulties with existing screening assays; 3) Exposure of the human population to the blood sucking insect vectors (Reduviid bugs) is more limited than in third world countries, limiting infection; and 4) The biochemistry or behavior of the local insect vectors is less conducive to transmission of the disease to humans. The relative importance of each of these possibilities will be evaluated in the context of a region of western Texas located on the border with Mexico and known to have a well established sylvatic cycle of T. cruzi (30% of captured reduviid bugs contain trypanosomes) in close proximity to human habitation. Indigenous strains of T. cruzi will be collected from this region and established in culture for use in genotyping, to determine the variety of parasite strains and their potential relationship to known disease causing strains, and virulence testing. In addition, a cohort of volunteers from this region with a history of multiple reduviid bug bites, indicating close association with the insect vector is being assembled, and their sera will be screened for reactivity against different strains and stages of T. cruzi. These studies will contribute to our understanding of the current potential for human infection as well as the possibility of future risk of disease due to importation of new parasite strains into the western Texas border region.